(R)-(+)-1-Phenylethyl isocyanate → (S)-2-{[(3S,8S)-3-(4-Cyclohexylmethoxy-phenyl)-7-((R)-1-phenyl-ethylcarbamoyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid

HRID 391973Notes

Reaction equation

HRID 391973 reaction equation
C[O:2][C:3](=[O:51])[C@@H:4]([NH:20][C:21]([C@@H:23]1[CH2:32][C:31]2[CH:30]=[C:29]3[O:33][CH2:34][C@H:35]([C:37]4[CH:42]=[CH:41][C:40]([O:43][CH2:44][CH:45]5[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]5)=[CH:39][CH:38]=4)[O:36][C:28]3=[CH:27][C:26]=2[CH2:25][NH:24]1)=[O:22])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([CH3:18])[C:13]=2[CH3:19])=[CH:8][CH:7]=1.[N:52]([C@@H:55]([C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)[CH3:56])=[C:53]=[O:54]>C(Cl)Cl>[CH:45]1([CH2:44][O:43][C:40]2[CH:41]=[CH:42][C:37]([C@H:35]3[CH2:34][O:33][C:29]4=[CH:30][C:31]5[CH2:32][C@@H:23]([C:21]([NH:20][C@@H:4]([CH2:5][C:6]6[CH:7]=[CH:8][C:9]([C:12]7[CH:17]=[CH:16][N:15]=[C:14]([CH3:18])[C:13]=7[CH3:19])=[CH:10][CH:11]=6)[C:3]([OH:2])=[O:51])=[O:22])[N:24]([C:53](=[O:54])[NH:52][C@@H:55]([C:57]6[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=6)[CH3:56])[CH2:25][C:26]=5[CH:27]=[C:28]4[O:36]3)=[CH:38][CH:39]=2)[CH2:46][CH2:47][CH2:48][CH2:49][CH2:50]1

Participants

4

Reactant 2

HCID 7018262(R)-(+)-1-Phenylethyl isocyanateHCID 58327202(S)-2-{[(3S,8S)-3-(4-cyclohexylmethoxy-phenyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid methyl ester

Product 1

HCID 58327192(S)-2-{[(3S,8S)-3-(4-Cyclohexylmethoxy-phenyl)-7-((R)-1-phenyl-ethylcarbamoyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-2-{[(3S,8S)-3-(4-cyclohexylmethoxy-phenyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid methyl ester in DCM was added ((R)-1-isocyanato-ethyl)-benzene (5 eq.) and the reaction was stirred at room temperature for 1 hour. The reaction mixture was directly purified over silica (hexanes to 1:1 hexanes EtOAc to 1:1 hexanes EtOAc+1% MeOH to 1:1 hexanes EtOAc+2% MeOH to 1:1 hexanes EtOAc+3% MeOH). The resulting compound was hydrolyzed according to General Procedure B to give the title compound. LCMS (m/z): 824.

Workup

  1. customThe reaction mixture was directly purified over silica (hexanes to 1:1 hexanes EtOAc to 1:1 hexanes EtOAc+1% MeOH to 1:1 hexanes EtOAc+2% MeOH to 1:1 hexanes EtOAc+3% MeOH)

Sources & evidence

ORD record
ord-a33151899a3f4262ab435a4a398e3a51
Source dataset
uspto-grants-2013_02
Patent number
US08383644B2

Reaction notes

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